Novel MC1R variants in Ligurian melanoma patients and controls

Several variant forms of the melanocortin-1 receptor gene (MC1R) have been associated with red hair, fair skin and an increased risk for melanoma. Their involvement in melanoma susceptibility is apparently linked both to skin sensitivity and to non-pigmentary pathways. We investigated the frequency of the MC1R variants in the Italian region of Liguria, where the occurrence and penetrance of melanoma are low and primary susceptibility is characterized by prevalence of the CDKN2A c.301G>T [p.G101W] founder mutation. Additionally, we attempted to establish the frequency of the red hair/fair skin phenotype in our region. As predicted by anecdotal evidence, the frequency of red hair/phototype I was very low (0.7%). Screening of 17 red-haired individuals and their red-haired relatives, 207 controls and 214 melanoma patients unselected for hair color but all of Ligurian descent, led to the detection of 8 novel substitutions (c.133T>C [p.F45L], c.248C>T [p.S83L], c.332C>T [p. A111V], c.479G>A [p.R160Q], c.637C>T [p.R213W], c.793G>A [p. V265I], c.923C>T [p. T308M], c.943T>C [p.C315R]), 1 novel deletion (c.520_523delGTC [p.V174del]) and 3 novel synonymous variants (c.366G>C [p. V122V], c.684G>A [p. Q228Q], c.726C>T [p.T241T]). Preliminary genotype/phenotype correlation seems to indicate that other genes involved in the regulation of human pigmentation may mask the recessive action of high-penetrance MC1R alleles, thus determining the low frequency of at-risk phototypes and of incidence and/or penetrance of melanoma in Liguria.     

Comparative study of marginal zone lymphoma involving bone marrow

Few studies have characterized or compared the pathologic features of bone marrow involvement by extranodal (EMZL), splenic (SMZL), and nodal marginal zone lymphoma (NMZL). We evaluated 45 bone marrow biopsy specimens from 39 patients with marginal zone lymphomas. As previously reported, bone marrow involvement was frequent (100%) in patients with SMZL. We also identified lymphoma involving bone marrow in 11 (44%) of 25 patients with EMZL and 1 of 2 patients with NMZL. The patterns of infiltration were mixed in all groups; however, the extent of involvement was greater in SMZL than in EMZL. In addition, germinal centers were present in bone marrow biopsy specimens involved by lymphoma in 4 patients with SMZL. Intrasinusoidal infiltration was common (10/12 [83%]) and prominent in patients with bone marrow involvement by SMZL, but was not invariably present. Intrasinusoidal infiltration of the bone marrow also was not specific for SMZL since similar infiltrates, although subtle, also were found in patients with other small B-cell lymphoproliferative disorders, including 6 (55%) of 11 patients whose bone marrow samples were infiltrated by EMZL.     

Profilin-mediated food-induced allergic reactions are associated with oral epithelial remodeling

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Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming

Naive T cells are stimulated by antigen-presenting dendritic cells (DCs) in secondary lymphoid organs, but whether other types of cell participate in T cell priming is unclear. Here we show in mice that natural killer (NK) cells, which are normally excluded from lymph nodes, are rapidly recruited in a CCR7-independent, CXCR3-dependent manner to lymph nodes on stimulation by the injection of mature DCs. Recruitment of NK cells is also induced by some, but not all, adjuvants and correlates with the induction of T helper cell type 1 (T(H)1) responses. NK cell depletion and reconstitution experiments show that NK cells provide an early source of interferon-gamma (IFN-gamma) that is necessary for T(H)1 polarization. Taken together, our results identify an induced pathway of NK cell migration in antigen-stimulated lymph nodes and a mechanism by which some adjuvants may facilitate T(H)1 responses.     

The restorative effect of naps on perceptual deterioration

Human performance on visual texture discrimination tasks improves slowly (over days) in the absence of additional training. This 'slow learning' requires nocturnal sleep after training and is limited to the region of visual space in which training occurred. Here, we tested human subjects four times in one day and found that with repeated, within-day testing, perceptual thresholds actually increased progressively across the four test sessions. This performance deterioration was prevented either by shifting the target stimuli to an untrained region of visual space or by having the subjects take a mid-day nap between the second and third sessions.     

Invasion profiles of Brazilian field isolates of Plasmodium falciparum: phenotypic and genotypic analyses

The invasion of red blood cells (RBCs) by Plasmodium falciparum is dependent on multiple molecular interactions between erythrocyte receptors and parasite ligands. Invasion studies using culture-adapted parasite strains have indicated significant receptor heterogeneity. It is not known whether this heterogeneity reflects the parasite invasion arsenal in the field. We have studied the invasion phenotypes of 14 distinct field isolates from the Legal Amazon areas of Brazil by using erythrocyte invasion assays to investigate invasion into normal, enzyme-treated, and clinical-mutant RBCs. Analysis of these isolates revealed four distinct invasion profiles. Using En(a-) cells to get an unequivocal estimate of the use of glycophorin A (GPA) as a receptor, we found that the 175-kDa erythrocyte-binding antigen (EBA-175)/GPA pathway was used by a minority of the parasite isolates studied. Although polymorphism of region II domains at specific amino acid positions in both EBA-140 and EBA-181 was found in these field isolates, this did not correlate with invasion profiles and thus receptor selectivity. These studies have further confirmed the existence of a significant diversity of invasion pathways in nature and suggest that additional parasite ligands will have to be targeted to devise global vaccines that will work in the field.